NOD2 is highly expressed in Behçet disease with pulmonary manifestations

Hamzaoui Kamel, Abid Hanadi, Berraies Anissa, Ammar Jamel, Hamzaoui, Hamzaoui Agnès

Description

Excessive Th1 cells and TLRs functions are involved in the pathogenesis of Behcet's disease (BD) in response to bacterial antigens. NOD2, an intracellular pathogen recognition sensor, modulates innate defence to muropeptides derived from various bacterial species. To further define a role for NOD2 in BD, we analysed NOD2 transcriptional responses in BAL-MNC from BD patients with pulmonary manifestations. Methods We analysed NOD1, NOD2, T-bet and TLRs mRNA expression with real-time polymerase chain-reaction in BAL cells obtained from 23 BD patients with pulmonary manifestations and their matched controls. Results We found that NOD2 mRNA expression was highly up-regulated in BAL cells from BD and sarcoidosis patients compared to healthy control group ( P = 0.001 ). In BD patients, significant correlation was found between NOD2 and T-bet mRNA expression (r = 0.602; P = 0.0009 ). In BAL from BD patients, NOD2 and T-bet mRNA expression were significantly correlated with BAL-lymphocytes (r = 0.485, P = 0.010 ; r = 0684, P = 0.0001 respectively ). NOD2 in BD was also correlated with TLR 2(r = 0.444; P = 0.021 ) and TLR 4 (r = 0.574; P = 0.001 ) mRNA expression. Conclusion Our results indicate that BAL-MNC from BD patients expressed NOD2 as a result of lung inflammation. TLRs and NOD2 synergize for the induction of proinflammatory cytokines. BAL inflammatory cells showed an increased Th1 situation as indicated by increased T-bet mRNA expression.

Sujets

• NOD2
• Récepteur de type Toll
• TBX21
• Behçet's disease
• Inflammation

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 10
• Langue: English

Extrait

Hamzaouiet al.Journal of Inflammation2012,9:3 http://www.journalinflammation.com/content/9/1/3

R E S E A R C HOpen Access NOD2 is highly expressed in Behçet disease with pulmonary manifestations 1* 22 22 Kamel Hamzaoui, Hanadi Abid , Anissa Berraies , Jamel Ammarand Agnès Hamzaoui

Abstract Background:Excessive Th1 cells and TLRs functions are involved in the pathogenesis of Behcet’s disease (BD) in response to bacterial antigens. NOD2, an intracellular pathogen recognition sensor, modulates innate defence to muropeptides derived from various bacterial species. To further define a role for NOD2 in BD, we analysed NOD2 transcriptional responses in BALMNC from BD patients with pulmonary manifestations. Methods:We analysed NOD1, NOD2, Tbet and TLRs mRNA expression with realtime polymerase chainreaction in BAL cells obtained from 23 BD patients with pulmonary manifestations and their matched controls. Results:We found that NOD2 mRNA expression was highly upregulated in BAL cells from BD and sarcoidosis patients compared to healthy control group (P=0.001). In BD patients, significant correlation was found between NOD2 and Tbet mRNA expression (r = 0.602;P=0.0009). In BAL from BD patients, NOD2 and Tbet mRNA expression were significantly correlated with BALlymphocytes (r = 0.485,P=0.010; r = 0684,P=0.0001 respectively). NOD2 in BD was also correlated with TLR 2(r = 0.444;P=0.021) and TLR 4 (r = 0.574;P=0.001) mRNA expression. Conclusion:Our results indicate that BALMNC from BD patients expressed NOD2 as a result of lung inflammation. TLRs and NOD2 synergize for the induction of proinflammatory cytokines. BAL inflammatory cells showed an increased Th1 situation as indicated by increased Tbet mRNA expression. Keywords:NOD2, TLRs, Tbet, Behçet Disease, Inflammation

Background Behcet’s disease (BD) is a systemic vasculitis with unknown aetiology. Immune dysregulation involving T and B cells with hyperreactive neutrophils, supposedly triggered by infectious agents, contribute to disease pathogenesis in addition to genetic predisposition [13]. Documentation of various atypical streptococcal species in oral flora of BD patients, clinical flares after dental procedures, and a good response to antibacterial treat ment, have been considered as evidence for the role of Streptococcus in BD [4]. However, none of the microbial agents has been definitely proved to cause BD. Immuno logical disorders are important in BD pathogenesis [5]. T lymphocytes from patients with BD produced a parti cular inflammatory mediators pattern when stimulated

* Correspondence: [e-mail] 1 Division of Histology and Immunology, Department of Basic Sciences, Medicine School of Tunis, Tunis El Manar University, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia Full list of author information is available at the end of the article

with a bacterial superantigen [69]. Innate immunity was deeply investigated in BD patients [9,10]. Tolllike recep tor (TLR)expressing cells (TLR2 and TLR4) [9] and gamma delta T cells (TCRgδ) [11] have been involved in BD inflammatory reactions. NODlike receptors (NLRs) are a family of innate immune receptors that play key roles in host defence and inflammation. NLR genes have been preserved throughout evolution and at least 22 members are pre sent in humans [12]. NOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide (MDP), and variants of NOD2 are associated with chronic inflammatory diseases of barrier organs (e.g., Crohn’s disease, asthma, and atopic eczema) [12,13]. It is known that activation of NOD2 induces a variety of inflammatory and antibacterial factors. Truncated NOD2 proteins are encoded by mutations in the NOD2 gene that predispose individuals to inflammatory dis eases [14].

© 2012 Hamzaoui et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.